Topic:Cytokines
Cytokines are small proteins that are important in cell signaling and are produced by various cell types in horses, particularly during immune responses. These molecules facilitate communication between cells and play a role in regulating inflammation, immune function, and hematopoiesis. In horses, cytokines are involved in numerous physiological and pathological processes, including infection, inflammation, and wound healing. Examples of cytokines studied in equine research include interleukins, interferons, and tumor necrosis factors. Their expression levels can change in response to disease states, making them potential biomarkers for assessing equine health and disease progression. This page compiles peer-reviewed research studies and scholarly articles that explore the role, regulation, and clinical implications of cytokines in equine health.
New Evidence for the Mechanisms of Nanoplastics Amplifying Cadmium Cytotoxicity: Trojan Horse Effect, Inflammatory Response, and Calcium Imbalance. Nanoplastics (NPs) are emerging pollutants worldwide. Particularly worrisome is that although studies have reported that NPs can amplify the biotoxicity of environmental pollutants, the specific mechanism remains unclear. Here, we found that NPs, even without significant toxicity (cell survival: 99.11%), amplified the hepatocyte toxicity of Cd. Mechanistically, higher Cd uptake (Δ = 23.80%) combined with crucial intracellular desorption behavior of Cd loaded in NPs (desorption rate: 82.70%) were identified as prerequisites for NPs amplifying Cd cytotoxicity. As for toxigenic pathways, the inf...
In Vitro Immunomodulatory Effects of Equine Adipose Tissue-Derived Mesenchymal Stem Cells Primed with a Cannabidiol-Rich Extract. Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrati...
Transcriptomic and Proteomic Profiling of Rabbit Kidney Cells Infected with Equine Herpesvirus 8. The present study investigated the host cell response to EHV-8 infection in rabbit kidney (RK-13) cells through transcriptomic and proteomic approaches. At 24 h post-infection, a total of 2118 differentially expressed genes (DEGs) were identified, with 1338 upregulated and 780 downregulated. At 48 h, 7388 DEGs were detected, with 4342 upregulated and 3046 downregulated genes. Proteomic analysis revealed 932 differentially expressed proteins (DEPs) at 24 h (364 upregulated and 568 downregulated) and 3866 DEPs at 48 h (2285 upregulated and 1581 downregulated). Of these, 237 upregulated and 336 d...
Influence of dietary Saccharomyces cerevisiae fermentation product on markers of inflammation and cartilage metabolism in young exercising horses challenged with intra-articular lipopolysaccharide. The objective was to evaluate dietary fermentation product (SCFP) on joint inflammation and cartilage metabolism in exercising yearlings challenged with intra-articular lipopolysaccharide (LPS), hypothesizing dietary SCFP (TruEquineC, Diamond V Mills, Inc.) would ameliorate joint inflammation and increase cartilage metabolism. Thirty Quarter Horse yearlings were stratified by bodyweight (BW), age, sex, and randomly assigned to dietary treatments (n = 10/treatment): control (0), 46, or 92 mg/kg BW/d SCFP. Treatments were top-dressed to 1% BW/d concentrate void of added microbials. Horses ...
Astaxanthin supplementation in Arabian racing horses mitigates oxidative stress and inflammation in peripheral blood mononuclear cells through enhanced mitophagy. Astaxanthin, a strong antioxidant carotenoid, has shown promising features in mitigating inflammation and oxidative stress and so that has been considered as a supplement for high-performance animals. In this study, we aimed to evaluate the effects of astaxanthin on oxidative stress, inflammation, and mitochondrial health in peripheral blood mononuclear cells (PBMC) isolated from Arabian racehorses. Horse-derived peripheral blood mononuclear cells exposed to hydrogen peroxide (H₂O₂) presented increased reactive oxygen species (ROS) accumulation and overexpression of pro-inflammatory cytoki...
Circadian Oscillation of Leukocyte Subpopulations and Inflammatory Cytokines over a 24-H Period in Horses. The objective of the present study was to investigate the influence of daily rhythms on the immune and inflammatory systems in horses, considering white blood cell count (WBCs), leukocyte subpopulations (neutrophils, basophils, eosinophils, lymphocytes, and monocytes), CD4+, and CD8+ lymphocyte populations, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Ten Italian Saddle horses (7-12 years old, body weight 480 ± 30 kg) underwent blood sampling every 4 h over a 24-h period. The COSINOR method was used to identify rhythms and their parameters. A one-way ...
MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma. Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils...
The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models. Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, chronic inflammation, and progressive joint dysfunction. Despite rising incidences driven by ageing and increasing obesity, potent treatments remain elusive, exacerbating the socioeconomic burden. OA pathogenesis involves an imbalance in extracellular matrix (ECM) turnover, mediated by inflammatory cytokines and matrix-degrading enzymes, leading to oxidative stress, chondrocyte apoptosis, and ECM degradation. Additionally, synovial inflammation (synovitis) plays a critical role in disease pro...
Identification of key genes in immune-response post-endurance run in horses. Intense physical activity in endurance horses triggers complex immune and inflammatory responses, yet the molecular mechanisms underlying these adaptations remain unclear. This study investigated immune-related transcriptomic changes following a 160 km endurance ride, focusing on sex-based differences. Using a bioinformatics approach, differentially expressed genes (DEGs), pathways, microRNAs (miRNAs), and transcription factors (TFs) were analyzed before (T0) and after (T1) the ride. A protein-protein interaction (PPI) analysis was conducted to identify key regulatory genes. Pathway enrichment...
Three-dimensional tissue culture supports the structure and function of equine synovial explants over 4 days. To evaluate the feasibility of short-term 3-D tissue culture in maintaining the structure and function of equine synovial explants and demonstrate that day 4 explant characteristics were not significantly different from day 0. We hypothesized that a 4-day culture period in 3-D explant culture would not significantly disrupt synovial tissue health and function compared to baseline measurements. Unassigned: Synovial explants (n = 24/horse) from healthy carpal joints of 5 horses were cultured in 12-well plates using tissue-stabilizing agar rings. Explants were evaluated in triplicate or quadrupli...
Equine bone marrow aspirate and bone marrow aspirate concentrate are enriched with interleukin-1 receptor antagonist protein. To analyze the cellular, growth factor, and cytokine composition of equine sternal bone marrow aspirate (BMA) and laboratory-centrifuged BMA concentrate (BMAC). Unassigned: This was an in vitro experimental study. Cellular composition, growth factors (IGF-I, VEGF, PDGF, TGF-β1), and cytokines (IL-6, IL-10, tumor necrosis factor-α (TNF-α), and IL-1 receptor antagonist protein [IL-1Ra]) were quantified using a standard automated hematology analyzer and ELISA methods, respectively, in donor-matched BMA, BMAC (in-house centrifugation protocol), whole blood, and platelet-rich plasma (E-PET; Pall...
Longitudinal Evaluation of Vitamin D, Parathyroid Hormone, Antimicrobial Peptides, and Immunomodulatory Genes in Hospitalized Foals. Information about the association of antimicrobial peptides with hypovitaminosis D in hospitalized foals is lacking. Objective: We aimed to longitudinally determine the association of serum concentrations of vitamin D metabolites, vitamin D binding protein (DBP), and parathyroid hormone (PTH) with antimicrobial peptides (β-defensin-1 and cathelicidin-1) and the mRNA expression of the vitamin D receptor (VDR), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), disease severity, and mortality in hospita...
Early effects of anti-TNFα antibodies in horses with osteoarthritis. Osteoarthritis (OA) is the most common pathology in sport horses, presenting a chronic and recurrent course. Traditional anti-inflammatory treatments provide only temporary clinical improvement and pain relief; however, they have been associated with metabolic disorders in articular cartilage in the medium term. In this study, we generated a llama polyclonal antibody against equine TNF-α, which was used for intra-articular treatment in horses with OA. Treatment effects were assessed through clinical examination and the determination of inflammatory parameters (MMP-2, MMP-9, LDH, and GAGs) in ...
Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon. Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated follow...
Interleukin-1β as an articular process joint intra-articular model induces synovitis and signs of acute neck pain in horses. To develop and define a model of acute neck pain in an equine cervical articular process joint (APJ) using recombinant equine IL-1β (reIL-1β). Unassigned: 12 horses in this experimental study received a randomly assigned, unilateral intra-articular injection of 50 ng (n = 6) or 100 ng (n = 6) of reIL-1β and saline (contralateral side as control) into the C5-to-C6 APJ. Blinded ultrasonographic, clinical, and biomechanical parameters were evaluated between 4 hours and 14 days. Unassigned: There was a significant increase in APJ effusion on ultrasonographic examination that peaked at 24 hours ...
The Anti-Inflammatory Effects of Liraglutide in Equine Inflammatory Joint Models. This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with ...
Equine autologous blood-based products contain variable quantities of transforming growth factor-β1, interleukin-1 receptor antagonist, and α2-macroglobulin. Quantify the concentration of α2-macroglobulin (A2M), immunomodulatory cytokines, and TGF-β1 factors in 4 commercially available autologous blood-based products including conditioned A2M (CA2M; Alpha2EQ; Astaria Global), autologous protein solution (APS; Pro-Stride; Zoetis), platelet-rich plasma (PRP; Restigen; Zoetis), and autologous conditioned plasma (ACP; Arthrex ACP). We hypothesized that CA2M would have higher concentrations of A2M and lower concentrations of cytokines and growth factors compared to APS, PRP, and ACP. Unassigned: Blood was obtained from 6 healthy, adult horses and proc...
Skin Barrier in Normal and Allergic Horses: What Do We Know? Information on skin barrier in horses is limited. A study on the epidermal ultrastructure of normal and allergic horses documented disorganized amorphous intercellular lipids in the stratum corneum of allergic samples. These findings are similar to atopic canine and human skin. Currently, there is no published study comparing skin barrier function parameters between normal and allergic horses; thus, the functional implications of the ultrastructural changes are unknown. In normal horses, body location, gender, breed, and ambient conditions affect skin barrier parameters, such as Transepidermal...
Molecular Assessment of Plasma Concentrations of Selected Adipokines and IL-8 in Horses with Back Pain and Comorbid Asthma-Based on Clinical Cases. Similarly, in humans and horses, thoracic and lumbosacral back pain cause more disability and work interruptions worldwide than any other disease. Given that there are few effective treatments for back pain in humans and animals, primary prevention strategies and a reduction in pain factors may be crucial. In the analysed data obtained for the horses studied, the pattern of changes in adipocytokine concentrations, including resistin, visfatin and leptin, was noted for those with back pain compared to the control animals. Concentrations of selected adipocytokines in horses from the back pain gr...
A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis. Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases. Topical administration of SOCS1-KIR, a peptide mimic of SOCS1, was previously correlated to reduced ocular pathologies within ERU patients. Unassigned: To further assess the translational potential of a SOCS1 mimetic to treat RU, we assessed peptide-mediated modulatio...
Positive correlation between interleukin (IL) 1 beta to IL-1 receptor antagonist levels in Standardbred racehorses prior to racing. Interleukin 1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) are both upregulated following traumatic injury. As IL-1RA blocks inflammatory signaling by IL-1β, overexpression of IL-1β relative to IL-1RA may drive inflammatory diseases. As such, determination of the relationship between IL-1β to IL-1RA expression levels in horses may provide insight into disease states or serve as a therapeutic readout of response to medical interventions. As techniques to detect plasma concentrations of IL-1β and IL-1RA in horses lack sensitivity, we developed and validated novel enzyme-linked immunos...
Stress, lipid profile and inflammatory responses to flunixin meglumine administration in surgical and non-surgical castration in donkeys. Donkeys are in the Equidae family but have several differences from horses. There are many studies on the pathophysiology of pain and its clinical signs in horses, but data are limited for donkeys. Therefore, the present study aimed to investigate biochemical effects of flunixin meglumine in donkeys subjected to pain induced by bloodless and surgical castration. Twenty healthy male donkeys were randomly divided into four groups: 1- Surgical castration with flunixin injection, 2- Surgical castration without flunixin injection, 3- Non-surgical castration with flunixin injection, and 4- Non-surgi...
Correlation of fecal microbiome dysregulation to synovial transcriptome in an equine model of obesity associated osteoarthritis. Osteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immun...
Comparison of long and short rest periods during high-intensity interval exercise on transcriptomic responses in equine skeletal muscle. The purpose of this study was to elucidate the skeletal muscle transcriptomic response unique to rest duration during high-intensity interval exercise. Thoroughbred horses performed three 1-min bouts of exercise at their maximal oxygen uptake (10.7-12.5 m/s), separated by 15 min (long) or 2 min (short) walking at 1.7 m/s. Gluteus medius muscle was collected before and at 4 h after the exercise and used for RNA sequencing. We identified 1,756 and 1,421 differentially expressed genes in response to the long and short protocols, respectively using DEseq2 analysis [false discovery rate (FDR) cutof...
Effect of a dietary nutraceutical “STRUCTURE-Joint” on response of horses to intra-articular challenge with IL-1: implications for tissue adaptation to stress. The purpose was to determine local (articular) and systemic effects of intra-articular interleukin-1 in horses supplemented with a dietary PUFA supplement [STRUCTURE-Joint (ST-J)]. Sixteen (16) healthy, mature, light breed horses were randomly assigned to diets containing 0 or 120 mL (n = 8 per group) of ST-J for 30 d. On days 0 (prior to beginning supplementation) and 27, recombinant equine interleukin-1β (reIL-1 β) (75 ng) was injected into the left or right intercarpal joint to induce mild, transient synovitis. Synovial fluid was obtained by aseptic arthrocentesis at postinjection hou...
Differential modulation of inflammatory cytokines by recombinant IL-10 in IL-1β and TNF-α ̶ stimulated equine chondrocytes and synoviocytes: impact of washing and timing on cytokine responses. Osteoarthritis (OA) remains a challenging joint disorder necessitating effective anti-inflammatory interventions. In this study, our primary objective was to establish an in vitro protocol that replicates the clinical investigation of anti-inflammatory drugs intended for OA management. Focusing on recombinant IL-10 (r.IL-10) as a potential anti-inflammatory treatment, we designed and implemented two distinct protocols to evaluate the efficacy of r.IL-10 in modulating chondrocyte and synoviocyte inflammation.The experimental design involved sequential stimulation with IL-1β and TNF-α for 24 ...
Horse Innate Immunity in the Control of Equine Infectious Anemia Virus Infection: A Preliminary Study. The mechanisms of the innate immunity control of equine infectious anemia virus in horses are not yet widely described. Equine monocytes isolated from the peripheral blood of three Equine infectious anemia (EIA) seronegative horses were differentiated in vitro into macrophages that gave rise to mixed cell populations morphologically referable to M1 and M2 phenotypes. The addition of two equine recombinant cytokines and two EIA virus reference strains, Miami and Wyoming, induced a more specific cell differentiation, and as for other species, IFNγ and IL4 stimulation polarized horse macrophages...
Antibody isotyping and cytokine profiling in natural cases of Burkholderia mallei infection (glanders) in equines. Immunological aspects of B. mallei infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum. Methods: The study was conducted on serum samples collected from 151 glanders positive equines which include horses (n = 134), mules (n = 16), and donkeys (n = 01). The IgM, IgG, IgA and IgG (T) titre were determined against recombinant antigens by indirect E...
Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics. Ethyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h a...
Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype. Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chond...